February 12, 2012
by Cathryn Delude

For roughly two thousand years, Chinese herbalists have treated Malaria using a root extract, commonly known as Chang Shan, from a type of hydrangea that grows in Tibet and Nepal. More recent studies suggest that halofuginone, a compound derived from this extract's bioactive ingredient, could be used to treat many autoimmune disorders as well. Now, researchers from the Harvard School of Dental Medicine have discovered the molecular secrets behind this herbal extract's power.

It turns out that halofuginone (HF) triggers a stress-response pathway that blocks the development of a harmful class of immune cells, called Th17 cells, which have been implicated in many autoimmune disorders.

"HF prevents the autoimmune response without dampening immunity altogether," said Malcolm Whitman, a professor of developmental biology at Harvard School of Dental Medicine and senior author on the new study. "This compound could inspire novel therapeutic approaches to a variety of autoimmune disorders."

"This study is an exciting example of how solving the molecular mechanism of traditional herbal medicine can lead both to new insights into physiological regulation and to novel approaches to the treatment of disease," said Tracy Keller, an instructor in Whitman's lab and the first author on the paper.

This study, which involved an interdisciplinary team of researchers at Massachusetts General Hospital and elsewhere, will be published online February 12 in Nature Chemical Biology.

Prior research had shown that HF reduced scarring in tissue, scleroderma (a tightening of the skin), multiple sclerosis, scar formation and even cancer progression. "We thought HF must work on a signaling pathway that had many downstream effects," said Keller.

In 2009, Keller and colleagues reported that HF protects against harmful Th17 immune cells without affecting other beneficial immune cells. Recognized only since 2006, Th17 cells are "bad actors," implicated in many autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis and psoriasis. The researchers found that minute doses of HF reduced multiple sclerosis in a mouse model. As such, it was one of a new arsenal of drugs that selectively inhibits autoimmune pathology without suppressing the immune system globally. Further analysis showed that HF was somehow turning on genes involved in a newly discovered pathway called the amino acid response pathway, or AAR.

Scientists have only recently appreciated the role of the nutrient sensing-AAR pathway in immune regulation and metabolic signaling. There is also evidence that it extends lifespan and delays age-related inflammatory diseases in animal studies on caloric restriction. A conservationist of sorts, AAR lets cells know when they need to preserve resources. For example, when a cell senses a limited supply of amino acids for building proteins, AAR will block signals that promote inflammation because inflamed tissues require lots of protein.

"Think about how during a power outage we conserve what little juice we have left on our devices, foregoing chats in favor of emergency calls," said Whitman. "Cells use similar logic."

For the current study, the researchers investigated how HF activates the AAR pathway, looking at the most basic process that cells use to translate a gene's DNA code into the amino acid chain that makes up a protein.

The researchers were able to home in on a single amino acid, called proline, and discovered that HF targeted and inhibited a particular enzyme (tRNA synthetase EPRS) responsible for incorporating proline into proteins that normally contain it. When this occurred, the AAR response kicked in and produced the therapeutic effects of HF-treatment.

Providing supplemental proline reversed the effects of HF on Th17 cell differentiation, while adding back other amino acids did not, establishing the specificity of HF for proline incorporation. Added proline also reversed other therapeutic effects of HF, inhibiting its effectiveness against the malaria parasite as well as certain cellular processes linked to tissue scarring. Again, supplementation with other amino acids had no such effect. Such mounting evidence clearly demonstrated that HF acts specifically to restrict proline.

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29 comments

As a devotee of naturopathy, I love these kinds of discoveries. Mainstream (allopathic) medicine is being forced to reckon with thousands of years of real-world applications of natural medicine, time-tested by millions of those cured. Not only Chinese medicine, but also holistic, Ayurvedic, homeopathic, osteopathy, folk medicine and numerous other forms of healing that people are turning to in droves. Why? Because it works as well or better than conventional medicine and is most likely gentler on the human system. That's not to say it replaces conventional medicine, but again, it forces doctors to pay heed to practices like prevention and nutrition versus just prescription.

My toothache remedy - the worse the toothache the better it gets - involves vigorous brushing of the affected area including the cavity and the teeth and gums around and up and down, etc. with a tootbrush thoroughly doused with hydrogen peroxide USP 3% that you can buy cheap at the drugstore. Rinse, repeat, etc and so on. It can't hurt you, but if you're worried just rinse and spit, and don't do it more than a couple of times a day. You're good to go within a day and a half, guaranteed.

In fact, yes, it is a natural approach to tooth infection. I use it everyday to prevent gum disease by brushing with hydrogen peroxide. My dentist once asked himself aloud why I didn't have the problems his other patients had. I took that as a sign that I was doing something right. So congrats, just do it everyday to keep the dentist away. Whitens your teeth a bit also.

Whoa, whoa, whoa. You need to categorize a bit more. Homeopathy in absolutely no sense of the word is even a smidgen viable. Do you even know what homeopathy is?

Agreed, also consider the large number of chinese medicines that abuse and destroy the natural world. Many different remedies require bones, horns, etc of endangered animals, or the skulls of ancient animals. 'You know what they call 'alternative medicine' thats been proved to work?'

Chemicals are chemicals. It just doesn't matter where they come from, a lab, a bacteria tank, or a ancient herbal root used for 2000 years by traditional Chinese practitioners. Other forms of alternative medicine may in fact be useful, or they may be completely bogus (ex. homeopathy), but traditional herbal remedies all fall under the heading of using medicines to treat disease.

This is the basic foundation of so-called western pharmacological medicine.

Parsec- there are no such thing as chemicals. That is just a man-made classification for something. There are as many chemicals in you as there are in the environment around you. Chemicals, chemicals, chemicals...

Homeopathy could very well be the first use of quantum phenomena in medicine, in that its ingredients are impressed energetically on an inert medium. You all know too little about its successes to blanketly condemn it as a failure. That makes you lousy researchers and scientists.

As a little history lesson, there is an ugly story to the demise of homeopathy which had enjoyed decades of success prior to the dictum of the medical mafia of Johns-Hopkins, who banned all M.D.'s from using anything but the protocols of the hospital. There's a backstory to every bit of propaganda you've been force fed.

I enjoy studying chinese medicine for its approach to the human body and health. I never get into the herbs. In terms of studying treatment, i just focus on massage and on dietetics. An example of dietetics is that in Chinese Medicine, they recommend not eating too many apricots at a time, because it can cause "Shang Huo" which means Up Burn, or something like that. The meaning of this "Upburn" is that you are all dried out and heated up inside, and your GI tract and face and skin are inflamed. You can imagine what it is easily if you try. The Chinese say too many apricots can cause it along with a very many other things too. It is a very interesting and compelling system, but it should be considered cautiously just like anything else. One of the biggest oddities that has to be swallowed to accept Chinese Medicine is the notion of Qi. You have all heard of it. When i translate it, my preferred translation is "Effect" with a capital E.

The Chinese were ingenious practitioners, who developed a map of the "meridians" or energetic lines of the body. The use of acupuncture, once ridiculed by Westerners, is now prescribed by many doctors for difficult or frustrating cases that don't respond to conventional treatments.

"By 1914, Dr. Robert Allen in the Journal of the American Medical Association could state, with slight exaggeration, that "there is scarcely a city in the country in which medical societies have not issued edicts against members who accept contracts for lodge practice." Some societies, such as the Security Benefit Association, responded to this pressure by building self-contained hospitals. They too, however, often ran afoul of medical society pressure as well as a federal tax code that discriminated in favor of third-party insurance."http://www.herita...re-stateLook at this, doctors hung by their own petard thanks to the 'progressives'.

Whoa, whoa, whoa. You need to categorize a bit more. Homeopathy in absolutely no sense of the word is even a smidgen viable. Do you even know what homeopathy is?

Agreed, also consider the large number of chinese medicines that abuse and destroy the natural world. Many different remedies require bones, horns, etc of endangered animals, or the skulls of ancient animals. 'You know what they call 'alternative medicine' thats been proved to work?'

Yes, "mainstream" medicine uses substances that are proven to work. There would be absolutely no sense for pharmaceutical companies in ignoring herbal remedies that work.

If such herbal remedies are not accepted by themedical authorities you should stay clear...some of those substances are actually harmful in the wrong doses, or intereferes with other nmedication you are taking.

ALWAYS consult with a doctor before you self-medicate herbal medicines while taking prescription drugs.

Every person trying natural medicine as a cure for cancer is no longer with us. Natural medicine definitely has its place but not when lined up against hard core diseases.

Not true. Read about Gerson Therapy or Dr. Burzynski's anti-neoplaston protocol and you'll find plenty of cancer survivors, or you can continue to believe the cancer industry's smear campaign, whose multi-billion dollar per year chemo business is at stake.

"If such herbal remedies are not accepted by the medical authorities you should stay clear...some of those substances are actually harmful in the wrong doses, or intereferes with other nmedication you are taking."- Birger And what about the tens of thousands of people who died from taking prescription drugs? Or the class action suits against the pharmaceutical companies that make Vioxx, Celebrex, and others that either killed or maimed (thalidomide) patients. The alternative medicine record has only a few mishaps when compared to pharmaceuticals, and usually symptoms reverse when stopped.

Any "alternative" medicine that is proven to work is simply called medicine... it graduates from one label to the other when it is found to be effective. The same thing goes for "supernatural"... if something is known to be real it is called "natural", supernatural is a label that basically means "not known to be real".

Oh, really? I see you've rated my post as "aroc91", the first time ever, and I don't see any ratings by "ORAC", which ordinarily there would be. You're a prevaricator, and you're still disgusting.

If you knew how to read, you'd know that orac despises Ethelred. I happen to like him. That's completely beside the fact that using an obvious anagram as an alt is absolutely stupid. Why don't you get in touch with the administrators to confirm with their IP logs. It's not difficult to do.

The irony in you calling me a liar is delicious. You're the one lying through your teeth because I have no motive and you have no proof.

Which is beside the fact that I normally don't give a shit about ratings. The only person I consistently rate low is kevin.

Here's where it all began: Dec 10, 2011 "I, unlike these other buffoons, understand well what rawa is referring to and I applaud his original interpretation of works by others, especially David Deutsch, proponent of MWI, which is steadily becoming adopted by the physics establishment. I ask the rest of you, with your parochial and "yesteryear's news" viewpoints, especially in the light of quantum entanglement and 2D universes- What are you doing here?"-Telekinetic

"I'm reading about rat decision making, not aether foam wave bullshit. He's seriously talking about telepathy and dowsing, you moron. DOWSING. The idea that underground water can make a stick in your hand move. How dense do you have to be to take that seriously?" - aroc91/ORAC

There's my PROOF. When someone declares their innocence by saying "you have no proof", that usually comes out of the mouth of a criminal.

"I seem to be consistently rated one star by an "orac" who, according to his profile, has yet to make a comment. Is this what's known as a sock puppet? I thought for a moment that it was an anagram of the poster named "aroc91", but then no one would be that stupid or obvious."- Telekinetic Jan.15

"That's completely beside the fact that using an obvious anagram as an alt is absolutely stupid."- aroc91/ORAC (today)

You're such a nincompoop, you don't even realize you copied my sarcastic post word for word and are now using it to defend yourself!